CN101242808A - Compositions and methods for emulsifying a perfluorocarbon with an oxygen-carrying surfactant - Google Patents
Compositions and methods for emulsifying a perfluorocarbon with an oxygen-carrying surfactant Download PDFInfo
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Abstract
A physiologically acceptable perfluorocarbon emulsion composition includes perfluorodecalin and an oxygen-carrying fluorinated surfactant forming a stable emulsion in a continuous aqueous phase. The oxygen-carrying fluorinated surfactant may be fractionated to increase its physiological compatibility, and may further include a fatty acid radical perfluorinated to increase its oxygen-carrying capacity. The perfluorocarbon emulsion composition of the present invention thus exhibits improved stability and efficiency, broadening its application and effectiveness as an artificial oxygen carrier..
Description
Background of invention
Invention field
The present invention relates to perfluocarbon emulsion, more particularly, relate to compositions and with taking oxygen surfactant emulsifying perfluocarbon to generate the method for the carrier of oxygen in the physiologically acceptable blood vessel.
Description of related art
As worldwide,, make the U.S. increasing for the demand of blood along with the casual labour who nurses the baby closes on retirement age and the foreign inevitable casualties of conflicting and being caused.The patient that the victim of contingency and burn, cancer patient and other undergo surgery with medical treatment also needs a large amount of blood and blood products every day.In fact, just there is a people to need blood transfusion among per 20 Americans in a certain moment of their life.
For the wretched insufficiency of surprising and continuous demand of blood and blood supply donor, make to obtain the valuable target that physiologically acceptable dextran goods become biomedical research, particularly in the last few years.Perfluocarbon is chemically inert synthetic molecules, and it mainly is made up of carbon and fluorine atom, and has formed colourless liquid.Because they have the physical dissolution significant quantity gas ability of (comprising oxygen and carbon dioxide), thereby to make perfluocarbon appear to be the reasonable succedaneum of blood.Yet although have the performance of such gentleness (affable), perfluocarbon is hydrophobic, makes itself and water not miscible thus.Therefore, perfluocarbon must carry out emulsifying before intravenous uses.
During the Vietnam War, army is devoted to develop the blood substitute based on hemoglobin that is used for battlefield use.In identical therewith period, Leland doctor Clark of Cincinnati children's hospital at first uses perfluocarbon to begin to experimentize as alternative dextran goods.Although army is acceptable clinically based on not success immediately aspect the blood substitute of hemoglobin in exploitation, but causing Japanese Green Cross company to produce Fluosol DA by the previous work that doctor Clark, Robert Geyer, Henry Sloviter and other people carried out---it is the pure synthetic oxygen carrier of the first generation, demonstrates feasible human prospect.
Yet the problem of Fluosol DA is that the perfluocarbon emulsion of aqueous phase is unstable inherently aspect thermodynamics and kinetics.This unstability requires to store Emulsion with freezing state, and further needs before use immediately Emulsion and other assisted solutions is blended not only consuming time but also consume the process of power.In addition, during using Fluosol DA treatment, the oxygen supply of capacity and exchange need maintain the patient oxygen of 70-100%.
The synthetic oxygen carrier of the second filial generation is improved Fluosol DA, and it has utilized less perfluocarbon strand so that the described perfluocarbon of emulsifying more effectively, thereby allows to have the activating agent of higher concentration in the Emulsion, and has stronger oxygen carrying capacity thus.Second filial generation Emulsion is also more stable than Fluosol DA, and it can significantly not descend at 4 ℃ of storage some months and activity.
Improve although have these, owing to having only about 0.16 μ m of diameter or the littler drop could be well tolerable by physiological system, thereby still there be huge technological challenge in manufacturing and stable synthetic oxygen carrier.In addition, not miscible in water based on the Emulsion of perfluocarbon, thereby it is unstable inherently.Also comprise extraneous component such as known emulsifying agents such as egg yolk lecithin and lecithin, and the harm of described extraneous component is as the stability of the final products of the intravenous carrier of oxygen.
Therefore, exist to compositions with taking the demand of oxygen surfactant emulsifying perfluocarbon with the method that generates the physiologically acceptable artificial carrier of oxygen.Advantageously, such compositions and method will produce meticulous perfluocarbon emulsion, and described Emulsion has affinity and the enhanced oxygen carrying capacity that the water of little particle diameter, perfluocarbon and Emulsion and perfluocarbon increase between mutually.This paper discloses and has required the such compositions and the right of method.
Summary of the invention
The present invention is the current state of the art of response, thus particularly respond this area by current obtainable, generate with surfactant emulsifying perfluocarbon that the compositions of the physiologically acceptable artificial carrier of oxygen and problem that method still can not solve fully and demand develop.Therefore, the present invention provides compositions and with the method for taking oxygen surfactant emulsifying perfluocarbon through exploitation, and described compositions and method have overcome multiple or whole in the shortcoming of this area discussed above.
Comprise perfluorodecalin and form the fluorizated oxygen surfactant of taking of the stable emulsion of described perfluorodecalin at successive aqueous phase according to the perfluorocarbon emulsion composition of certain embodiments of the invention.Perfluorodecalin can composition weight about 5% to about 85% between amount provide, and fluorizated take that the oxygen surfactant can composition weight about 5% to about 50% between amount provide.The fluorizated oxygen surfactant of taking can comprise 6 fatty acids to 12 carbon atoms, and in some embodiments, can carry out perfluorinate so that strengthen its oxygen carrying capacity.
In one embodiment, described perfluorocarbon emulsion composition comprises the soybean lecithin of taking the oxygen surfactant as fluorizated.In other embodiments, the described fluorizated oxygen surfactant of taking can comprise a kind of in phosphatldylcholine, the pure and mild PHOSPHATIDYL ETHANOLAMINE of phosphatidyl-4, wherein aforesaid each derive from soybean lecithin.
The method that is used to prepare described perfluorocarbon emulsion composition can comprise provides soybean lecithin, with fatty acid radical replace to soybean lecithin and fluoride fat acid group to generate the fluorizated oxygen surfactant of taking.Described then method can be included in that successive water internal emulsification is fluorizated takes oxygen surfactant and perfluorodecalin, so that generate the physiologically acceptable artificial carrier of oxygen.
In one embodiment, replace to the fatty acid radical of soybean lecithin and can comprise having about 12 carbochains to about 22 carbon atoms.In some embodiments, can carry out perfluorinate so that strengthen its oxygen carrying capacity to fatty acid radical.
Spread all over the mentioned feature of whole description, advantage or similarly term and do not mean that attainable all features of the present invention and advantage all should or all in any one embodiment of the present invention.On the contrary, the term of mentioning described feature and advantage is interpreted as being meant that the concrete feature, advantage or the characteristic that are described together with embodiment are included at least one embodiment of the present invention.Therefore, the discussion that spreads all over feature, advantage and the similar terms of whole description can refer to (but not necessarily) identical embodiment.
In addition, feature, advantage and characteristic described in the invention can any suitable mode be combined in one or more embodiments.Those skilled in the relevant art it should be understood that the present invention can implement outside the one or more concrete feature of particular or advantage.In other examples, additional features and advantage can be verified in certain embodiments, and needn't be present in all embodiments of the present invention.
According to subsequently explanation and appended claim, these features of the present invention and advantage will become more fully obviously, and perhaps it can be grasped by the practice of the present invention that hereinafter proposes.
Detailed Description Of The Invention
Spread all over whole description mentioned " embodiment ", " embodiment " or similar term, be meant that the special characteristic, structure or the characteristic that are described together with embodiment are included at least one embodiment of the present invention.Therefore, the phrase " in one embodiment " that spreads all over whole description and occurred, " in embodiments " and similarly term can all refer to (but not necessarily) identical embodiment.
In addition, feature, structure and characteristic described in the invention can any suitable mode be combined in one or more embodiments.In the following description, in order thoroughly to understand embodiment of the present invention, a large amount of concrete details are disclosed.But those skilled in the relevant art are understood that the present invention can implement outside one or more concrete details, or implement with other method, component, material etc.In other examples, unclear for fear of aspect of the present invention, do not show known structure, material or operation or it is not described in detail.
Be meant carbon-fluorine (flourine) chemical compound as the employed term of this description " perfluocarbon ", it is characterized in that high gas dissolving ability, low viscosity, chemical inertness and biologically inert.Term " fluoridized " is meant the organic structure that each wherein relevant with carbon atom hydrogen atom is all replaced by fluorine.
The present invention includes compositions and meet the method that physiological system uses the synthetic oxygen carrier of standard with generation with taking oxygen surfactant emulsifying perfluocarbon.Particularly, the synthetic oxygen carrier that produces according to certain embodiments of the invention can form stable meticulous Emulsion, nontoxic, the no mutagenicity of described Emulsion and compatible with hemocyte and epithelial cell, have inappreciaple pharmacology, physiology and biochemical activity, and secreted without change or the harmless metabolite of formation in physiological system.
According to the indication of the compositions and methods of the invention can comprise that acute surgery is lost blood, the islet cells viability/islet cells former (pre-islet cell) of high risk angioplasty, pancreas preservation, the transporting of transplanted tissue that comprises islet cells, diabetes is transplanted, enhancing, operation on retina, acute myocardial infarction, acute ischemic stroke, various shock syndrome and/or any other indication well known by persons skilled in the art of tumor radiosensitivity.
In fact, except in physiological system, using as blood substitute, the preservation of transplanted tissue during can being particularly advantageous for transporting according to compositions of the present invention.For example, the islet transplantation thing has the standardized potentiality of the blood sugar level of making, and has prevented the complication relevant with diabetes.But, the frangible character of islet cells mean in them the overwhelming majority gather in the crops, preserve, transport and subsequently migration process in tend to death.Therefore, it is most important for the final success of islet transplantation process to have the islets of langerhans preservation and a restoration methods of high islet yield.Can will come the islet cells of single layer of stored is carried out preservation as antiseptic solution according to compositions of the present invention, and thus by making the oxygen depletion to the minimum islet yield that improves.
Can comprise the perfluocarbon that contains active pharmaceutical ingredient according to compositions of the present invention.For example, in some embodiments, perfluocarbon can comprise fluoridized cyclic hydrocarbon.In one embodiment, perfluocarbon comprises at least a cis and the transisomer of perfluorodecalin, and described perfluorodecalin is a kind of inorganic molecule of well-characterized, its formula C that sees service
10F
18And molecular weight is 462.08.Perfluorodecalin is also referred to as ten octafluoros for decahydronaphthalenes, perflunafene and/or perfluoro decahydronaphthalenes, and its boiling point is 142 ℃, and fusing point is-10 ℃ to 142 ℃, and flash-point is 40 ℃, and is 1.917kg/l at 25 ℃ bulk density.Although perfluorodecalin is insoluble in water, the present invention utilizes perfluorodecalin to have low viscosity and small particle diameter as the embodiment of active pharmaceutical ingredient is verified, and to appear at naked eyes be meticulous, the stable Emulsion of physics homogeneous solution thereby facilitated.Can carry out purification for use in medical application to perfluorodecalin or other perfluocarbon.
In some embodiments, the included perfluorodecalin of Emulsion can be about 5 percent to percent 85 (5-85%) of composition weight.In other embodiments, described compositions can further comprise second active pharmaceutical ingredient, its example is as the second fluoridized cyclic hydrocarbon, and the wherein said second fluoridized cyclic hydrocarbon also exists with the amount between about 5 percent to percent 85 (5-85%) of composition weight.In yet another embodiment, as the more detailed description of hereinafter being carried out, perfluorodecalin or other main active pharmaceutical ingredients can completely or partially replace with the fluoridized or highly fluorinated oxygen surfactant of taking.
In fact, in certain embodiments, described compositions comprises having remarkable fluorine content and aqueous dispersion performance, the purified surfactant that can be used for medical application.In some embodiments, described surfactant shows is enough to make it to play the high oxygen carrying capacity of surfactant and active pharmaceutical ingredient dual-use function.Described surfactant can be by naturally occurring precursor substance (as lecithin), by the synthetic counter pair of lecithin derived material, or by any other material preparation well known by persons skilled in the art.In one embodiment, described surfactant comprises soybean lecithin, as Phospholipon 90 G.Soybean lecithin is the complex mixture of phospholipid, glycolipid, triglyceride, sterol and little fat acid, carbohydrate and sphingolipid.The main phospholipid composition of soybean lecithin comprises phosphatidylcholine (13-18%), PHOSPHATIDYL ETHANOLAMINE (10-15%), phosphatidylinositols (10-15%), phosphatidic acid (5-12%).
Can modify so that reduce the pseudo-additive that exists in the Emulsion the native state of naturally occurring lecithin (comprising soybean lecithin), described Emulsion indicates it is the synthetic oxygen carrier that is used as physiological system at sales counter.Although in most applications, the surfactant that can comprise composition weight about 5 percent to percent 85 (5-85%) changes but the amount that is included in the surfactant in the compositions can and depend on the concrete Emulsion character of being sought according to the concentration of active pharmaceutical ingredient.
In some embodiments, described surfactant can react to show with the water and the perfluocarbon of Emulsion with formation and have the derivant of the powerful compatibility mutually.In one embodiment, described surfactant comprise modified be used for strengthening with the perfluocarbon of Emulsion mutually and/or the lecithin fraction of the affinity of water.As the above description that soybean lecithin carried out with regard to mentioning especially, lecithin fraction can comprise, for example phosphatidylcholine, PHOSPHATIDYL ETHANOLAMINE, inositol, choline, cephalin and/or other lecithin fraction well known by persons skilled in the art.Can be by fluoridizing or coming lecithin fraction is modified by the ester group that adds the height aqueous dispersion to base molecule.In some embodiments, described lecithin fraction can comprise fluorizated phosphatidylcholine, PHOSPHATIDYL ETHANOLAMINE ester and/or its mixture.
In one embodiment, described surfactant prepares by making lecithin fraction phosphatidyl choline and the esterification of fluorizated fatty acid glycerine base.Particularly, fluorizated fatty acid radical can replace the glyceryl hydroxyl to choline, keeps phosphatidyl simultaneously.Alternatively, naturally occurring fatty acid composition can change into same ester with fluorizated aliphatic alcohol ester on the phosphatidylcholine.In a word, fatty acid or the aliphatic alcohol that is used for esterification can comprise about 6 to 8 carbon atoms.
Esterification according to certain embodiments of the invention can be implemented by preparing first solution, and described first solution comprises the C of about 10 (10%) weight
10Fluoridize or fluoridized acid, comprise the C of about 90 (90%) percent weight
20Fluoridized sour solvent, and comprise mineral acids such as all example hydrochloric acids of about percent 0.1 (0.1%) weight or sulphuric acid.Prepare described first solution by the moderate heat of using between about 50 to 60 degrees centigrade (50-60 ℃).Prepare second solution by making phosphatidylcholine be saponified into glyceryl phosphatidyl choline.Between about 50 to 60 degrees centigrade (50-60 ℃), realize esterification then, thereby bring out esterification by adding described second solution lentamente to described first solution.In other embodiments, can similarly carry out the esterification process of alcohol, except with the reaction of fluorizated aliphatic alcohol before need to remove the acid groups of choline step can omit.
Form the Emulsion that Emulsion can form the fluorizated fatty acid-esterified glyceryl phosphatidyl choline that comprises above preparation by adding an amount of water.Water yield scope can be between about 50 percent to percent 70 (50-70%) of for example composition weight.
Compositions according to certain embodiments of the invention can further comprise non-active ingredient, so that prevent that compositions is along with the degraded of time or promote the effective use of said composition in physiological system, described non-active ingredient such as anticoagulant, antiseptic, antioxidant and/or any other non-active ingredient well known by persons skilled in the art.For example, in one embodiment, described compositions comprises following active component and non-active ingredient:
| The composition title | g/47g | ％(w/w) | The g/ liter |
| Perfluorodecalin | 29.9920 | 63.738 | 879.58 |
| Phospholipon 90G (soybean lecithin) | 2.6980 | 5.734 | 79.12 |
| Glycine | 0.2993 | 0.636 | 8.78 |
| The EDTA disodium | 0.0061 | 0.013 | 0.18 |
| Sodium phosphate, monobasic, monohydrate, crystal | 0.0184 | 0.039 | 0.54 |
| Sodium phosphate, binary, anhydrous | 0.0024 | 0.005 | 0.07 |
| Water | 14.0392 | 29.836 | 411.73 |
The present invention can other concrete forms embody, and does not break away from the feature of its essence or essence.Described embodiment only all is considered in all respects with explaining but not limits.Therefore, scope of the present invention is by appended claim but not indicate by aforesaid explanation.Definition and all changes in the scope in the claim equivalence all are included in their scope.
Claims (20)
1. perfluorocarbon emulsion composition at physiologically acceptable continuous aqueous phase, described compositions comprises:
Perfluorodecalin; With
The fluorizated oxygen surfactant of taking, it forms the stable emulsion of described perfluorodecalin at described continuous aqueous phase.
2. perfluorocarbon emulsion composition according to claim 1, wherein said perfluorodecalin with described composition weight about 5% to about 85% between amount exist.
3. perfluorocarbon emulsion composition according to claim 1, wherein said fluorizated take the oxygen surfactant with described composition weight about 50% to about 70% between amount exist.
4. perfluorocarbon emulsion composition according to claim 1, the wherein said fluorizated oxygen surfactant of taking comprises having 6 fatty acids to 12 carbon atoms.
5. perfluorocarbon emulsion composition according to claim 1, the wherein said fluorizated oxygen surfactant of taking is fluoridized.
6. perfluorocarbon emulsion composition according to claim 1, the wherein said fluorizated oxygen surfactant of taking comprises soybean lecithin.
7. perfluorocarbon emulsion composition according to claim 6, the wherein said fluorizated oxygen surfactant of taking comprises the phosphatidylcholine that derives from described soybean lecithin.
8. perfluorocarbon emulsion composition according to claim 6, the wherein said fluorizated oxygen surfactant of taking comprises the phosphatidylinositols that derives from described soybean lecithin.
9. perfluorocarbon emulsion composition according to claim 6, the wherein said fluorizated oxygen surfactant of taking comprises the PHOSPHATIDYL ETHANOLAMINE that derives from described soybean lecithin.
10. perfluorocarbon emulsion composition that is suitable as the physiologically acceptable artificial carrier of oxygen, described compositions comprises:
Perfluorodecalin; With
Fluorizated soybean lecithin, it forms the stable emulsion of described perfluorodecalin at successive aqueous phase.
11. perfluorocarbon emulsion composition according to claim 10, wherein said perfluorodecalin with described composition weight about 5% to about 85% between amount exist.
12. perfluorocarbon emulsion composition according to claim 10, wherein said fluorizated soybean lecithin with described composition weight about 50% to about 70% between amount exist.
13. perfluorocarbon emulsion composition according to claim 10, wherein said fluorizated soybean lecithin comprises the phosphatidylcholine that derives from described soybean lecithin.
14. perfluorocarbon emulsion composition according to claim 13, wherein said phosphatidylcholine is fluoridized.
15. perfluorocarbon emulsion composition according to claim 10, wherein said fluorizated soybean lecithin comprises fatty acid.
16. perfluorocarbon emulsion composition according to claim 15, wherein said fatty acid comprise that having length is about 12 carbochains to about 22 carbon atoms.
17. a method that is used to prepare the perfluorocarbon emulsion composition that is suitable as the physiologically acceptable artificial carrier of oxygen, described method comprises:
Soybean lecithin is provided;
Fatty acid radical is replaced to described soybean lecithin;
Fluoridize described fatty acid radical to generate the fluorizated oxygen surfactant of taking; With
At described fluorizated oxygen surfactant and the perfluorodecalin taken of successive water internal emulsification, to generate the physiologically acceptable artificial carrier of oxygen.
18. method according to claim 17, wherein said soybean lecithin comprises a kind of in phosphatidylcholine, the pure and mild PHOSPHATIDYL ETHANOLAMINE of phosphatidyl-4, and each in wherein said phosphatidylcholine, the pure and mild PHOSPHATIDYL ETHANOLAMINE of phosphatidyl-4 derives from described soybean lecithin.
19. method according to claim 17 wherein replaces fatty acid radical to described soybean lecithin and comprises that selection has about 12 fatty acid radicals to the carbochain of about 22 carbon atoms.
20. method according to claim 17 is wherein fluoridized described fatty acid radical and is comprised the described fatty acid radical of perfluorinate.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11/190,433 US20070026024A1 (en) | 2005-07-27 | 2005-07-27 | Compositions and methods for emulsifying a pefluorocarbon with an oxygen-carrying surfactant |
| US11/190,433 | 2005-07-27 |
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| CN101242808A true CN101242808A (en) | 2008-08-13 |
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| CNA2006800304617A Pending CN101242808A (en) | 2005-07-27 | 2006-07-27 | Compositions and methods for emulsifying a perfluorocarbon with an oxygen-carrying surfactant |
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| US (1) | US20070026024A1 (en) |
| JP (1) | JP2009502956A (en) |
| CN (1) | CN101242808A (en) |
| BR (1) | BRPI0615985A2 (en) |
| CA (1) | CA2616986A1 (en) |
| MX (1) | MX2008001350A (en) |
| WO (1) | WO2007014328A2 (en) |
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| CN112972757A (en) * | 2021-03-05 | 2021-06-18 | 江苏菌均君隽生物科技有限公司 | Perfluorodecalin hydrogel healing-promoting dressing and preparation method and application thereof |
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| EP2373289A4 (en) | 2008-12-08 | 2014-07-02 | Univ Utah Res Found | Stable perfluorocarbon emulsion for use as an artificial oxygen carrier |
| US20100144597A1 (en) * | 2008-12-10 | 2010-06-10 | Ward Kevin R | Novel combinatorial approaches to enhancing oxygen transport to tissues |
| CN102625710A (en) | 2009-08-25 | 2012-08-01 | 艾格尼丝·奥斯塔芬 | Synthesis of oxygen carrying, turbulence resistant, high density submicron particulates |
| US10751464B2 (en) | 2009-08-25 | 2020-08-25 | Nanoshell Company, Llc | Therapeutic retrieval of targets in biological fluids |
| US10099227B2 (en) | 2009-08-25 | 2018-10-16 | Nanoshell Company, Llc | Method and apparatus for continuous removal of sub-micron sized particles in a closed loop liquid flow system |
| US11285494B2 (en) | 2009-08-25 | 2022-03-29 | Nanoshell Company, Llc | Method and apparatus for continuous removal of sub-micron sized particles in a closed loop liquid flow system |
| US8709451B2 (en) * | 2010-01-20 | 2014-04-29 | University Of Utah Research Foundation | Stable nanoemulsions for ultrasound-mediated drug delivery and imaging |
| CN102161769B (en) * | 2011-01-19 | 2013-01-23 | 上海三爱富新材料股份有限公司 | Water-based fluorine-containing polymer dispersed emulsion and stabilization method thereof |
| US11389451B2 (en) | 2017-09-12 | 2022-07-19 | Hyloris Developments S.A. | Metolazone emulsion formulation |
| WO2024046999A1 (en) * | 2022-08-31 | 2024-03-07 | Johann Wolfgang Goethe-Universität Frankfurt am Main | Lecithin-modified nanoscale oxygen carriers (lenox) |
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| US4252827A (en) * | 1979-05-23 | 1981-02-24 | The Green Cross Corporation | Oxygen-transferable fluorocarbon emulsion |
| US4423077A (en) * | 1982-07-27 | 1983-12-27 | The University Of Pennsylvania | Perfluorochemical emulsion artificial blood |
| GB8504916D0 (en) * | 1985-02-26 | 1985-03-27 | Isc Chemicals Ltd | Emulsions of perfluorocarbons in aqueous media |
| US5077036A (en) * | 1986-01-14 | 1991-12-31 | Alliance Pharmaceutical Corp. | Biocompatible stable fluorocarbon emulsions for contrast enhancement and oxygen transport comprising 40-125% wt./volume fluorocarbon combined with a phospholipid |
| US4900824A (en) * | 1986-08-25 | 1990-02-13 | International Therapeutics Inc. | Perfluoro hexamethylenetetramine useful in synthetic blood |
| US5243044A (en) * | 1986-08-25 | 1993-09-07 | International Therapeutics, Inc. | Compounds of perfluoro[3,3,3]propellene and perfluoro hexamethylenetetramine |
| US5628930A (en) * | 1992-10-27 | 1997-05-13 | Alliance Pharmaceutical Corp. | Stabilization of fluorocarbon emulsions |
| ES2244169T3 (en) * | 1998-02-09 | 2005-12-01 | Bracco International B.V. | ADDRESSED SUPPLY OF BIOLOGICALLY ACTIVE MEDIA. |
-
2005
- 2005-07-27 US US11/190,433 patent/US20070026024A1/en not_active Abandoned
-
2006
- 2006-07-27 MX MX2008001350A patent/MX2008001350A/en not_active Application Discontinuation
- 2006-07-27 WO PCT/US2006/029406 patent/WO2007014328A2/en active Application Filing
- 2006-07-27 JP JP2008524194A patent/JP2009502956A/en not_active Withdrawn
- 2006-07-27 BR BRPI0615985-0A patent/BRPI0615985A2/en not_active IP Right Cessation
- 2006-07-27 CA CA002616986A patent/CA2616986A1/en not_active Abandoned
- 2006-07-27 CN CNA2006800304617A patent/CN101242808A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111110875A (en) * | 2019-12-23 | 2020-05-08 | 哈尔滨医科大学 | PH and oxygen double-sensitive magnetic resonance imaging contrast agent and preparation method thereof |
| CN112972757A (en) * | 2021-03-05 | 2021-06-18 | 江苏菌均君隽生物科技有限公司 | Perfluorodecalin hydrogel healing-promoting dressing and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2009502956A (en) | 2009-01-29 |
| MX2008001350A (en) | 2008-09-09 |
| WO2007014328A2 (en) | 2007-02-01 |
| CA2616986A1 (en) | 2007-02-01 |
| BRPI0615985A2 (en) | 2011-05-31 |
| US20070026024A1 (en) | 2007-02-01 |
| WO2007014328A3 (en) | 2007-10-11 |
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